ID F6ZT77_ORNAN Unreviewed; 881 AA.
AC F6ZT77;
DT 27-JUL-2011, integrated into UniProtKB/TrEMBL.
DT 02-DEC-2020, sequence version 3.
DT 27-MAR-2024, entry version 71.
DE RecName: Full=Thyroid peroxidase {ECO:0000256|ARBA:ARBA00021693};
DE EC=1.11.1.8 {ECO:0000256|ARBA:ARBA00012311};
GN Name=TPO {ECO:0000313|Ensembl:ENSOANP00000015632.3};
OS Ornithorhynchus anatinus (Duckbill platypus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Monotremata; Ornithorhynchidae; Ornithorhynchus.
OX NCBI_TaxID=9258 {ECO:0000313|Ensembl:ENSOANP00000015632.3, ECO:0000313|Proteomes:UP000002279};
RN [1] {ECO:0000313|Ensembl:ENSOANP00000015632.3, ECO:0000313|Proteomes:UP000002279}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Glennie {ECO:0000313|Ensembl:ENSOANP00000015632.3,
RC ECO:0000313|Proteomes:UP000002279};
RX PubMed=18464734; DOI=10.1038/nature06936;
RA Warren W.C., Hillier L.W., Marshall Graves J.A., Birney E., Ponting C.P.,
RA Grutzner F., Belov K., Miller W., Clarke L., Chinwalla A.T., Yang S.P.,
RA Heger A., Locke D.P., Miethke P., Waters P.D., Veyrunes F., Fulton L.,
RA Fulton B., Graves T., Wallis J., Puente X.S., Lopez-Otin C., Ordonez G.R.,
RA Eichler E.E., Chen L., Cheng Z., Deakin J.E., Alsop A., Thompson K.,
RA Kirby P., Papenfuss A.T., Wakefield M.J., Olender T., Lancet D.,
RA Huttley G.A., Smit A.F., Pask A., Temple-Smith P., Batzer M.A.,
RA Walker J.A., Konkel M.K., Harris R.S., Whittington C.M., Wong E.S.,
RA Gemmell N.J., Buschiazzo E., Vargas Jentzsch I.M., Merkel A., Schmitz J.,
RA Zemann A., Churakov G., Kriegs J.O., Brosius J., Murchison E.P.,
RA Sachidanandam R., Smith C., Hannon G.J., Tsend-Ayush E., McMillan D.,
RA Attenborough R., Rens W., Ferguson-Smith M., Lefevre C.M., Sharp J.A.,
RA Nicholas K.R., Ray D.A., Kube M., Reinhardt R., Pringle T.H., Taylor J.,
RA Jones R.C., Nixon B., Dacheux J.L., Niwa H., Sekita Y., Huang X., Stark A.,
RA Kheradpour P., Kellis M., Flicek P., Chen Y., Webber C., Hardison R.,
RA Nelson J., Hallsworth-Pepin K., Delehaunty K., Markovic C., Minx P.,
RA Feng Y., Kremitzki C., Mitreva M., Glasscock J., Wylie T., Wohldmann P.,
RA Thiru P., Nhan M.N., Pohl C.S., Smith S.M., Hou S., Nefedov M.,
RA de Jong P.J., Renfree M.B., Mardis E.R., Wilson R.K.;
RT "Genome analysis of the platypus reveals unique signatures of evolution.";
RL Nature 453:175-183(2008).
RN [2] {ECO:0000313|Ensembl:ENSOANP00000015632.3}
RP IDENTIFICATION.
RC STRAIN=Glennie {ECO:0000313|Ensembl:ENSOANP00000015632.3};
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
CC -!- FUNCTION: Iodination and coupling of the hormonogenic tyrosines in
CC thyroglobulin to yield the thyroid hormones T(3) and T(4).
CC {ECO:0000256|ARBA:ARBA00003834}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H(+) + H2O2 + 2 iodide = diiodine + 2 H2O;
CC Xref=Rhea:RHEA:23336, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16240, ChEBI:CHEBI:16382, ChEBI:CHEBI:17606; EC=1.11.1.8;
CC Evidence={ECO:0000256|ARBA:ARBA00000959};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 [thyroglobulin]-3,5-diiodo-L-tyrosine + H2O2 =
CC [thyroglobulin]-dehydroalanine + [thyroglobulin]-L-thyroxine + 2 H2O;
CC Xref=Rhea:RHEA:48964, Rhea:RHEA-COMP:12276, Rhea:RHEA-COMP:12277,
CC Rhea:RHEA-COMP:12278, ChEBI:CHEBI:15377, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:90871, ChEBI:CHEBI:90872, ChEBI:CHEBI:90873; EC=1.11.1.8;
CC Evidence={ECO:0000256|ARBA:ARBA00000407};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[thyroglobulin]-3,5-diiodo-L-tyrosine + [thyroglobulin]-3-
CC iodo-L-tyrosine + H2O2 = [thyroglobulin]-3,3',5-triiodo-L-thyronine +
CC [thyroglobulin]-dehydroalanine + 2 H2O; Xref=Rhea:RHEA:48968,
CC Rhea:RHEA-COMP:12275, Rhea:RHEA-COMP:12276, Rhea:RHEA-COMP:12278,
CC Rhea:RHEA-COMP:12279, ChEBI:CHEBI:15377, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:90870, ChEBI:CHEBI:90871, ChEBI:CHEBI:90873,
CC ChEBI:CHEBI:90874; EC=1.11.1.8;
CC Evidence={ECO:0000256|ARBA:ARBA00000048};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[thyroglobulin]-3-iodo-L-tyrosine + H(+) + H2O2 + iodide =
CC [thyroglobulin]-3,5-diiodo-L-tyrosine + 2 H2O; Xref=Rhea:RHEA:48960,
CC Rhea:RHEA-COMP:12275, Rhea:RHEA-COMP:12276, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16240, ChEBI:CHEBI:16382,
CC ChEBI:CHEBI:90870, ChEBI:CHEBI:90871; EC=1.11.1.8;
CC Evidence={ECO:0000256|ARBA:ARBA00001533};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[thyroglobulin]-L-tyrosine + H(+) + H2O2 + iodide =
CC [thyroglobulin]-3-iodo-L-tyrosine + 2 H2O; Xref=Rhea:RHEA:48956,
CC Rhea:RHEA-COMP:12274, Rhea:RHEA-COMP:12275, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16240, ChEBI:CHEBI:16382,
CC ChEBI:CHEBI:46858, ChEBI:CHEBI:90870; EC=1.11.1.8;
CC Evidence={ECO:0000256|ARBA:ARBA00000658};
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC Evidence={ECO:0000256|ARBA:ARBA00001970};
CC -!- PATHWAY: Hormone biosynthesis; thyroid hormone biosynthesis.
CC {ECO:0000256|ARBA:ARBA00005197}.
CC -!- SUBUNIT: Interacts with DUOX1, DUOX2 and CYBA.
CC {ECO:0000256|ARBA:ARBA00011561}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000256|ARBA:ARBA00004479}; Single-
CC pass type I membrane protein {ECO:0000256|ARBA:ARBA00004479}.
CC -!- SIMILARITY: Belongs to the prostaglandin G/H synthase family.
CC {ECO:0000256|ARBA:ARBA00008928}.
CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of
CC feature annotation. {ECO:0000256|PROSITE-ProRule:PRU00076}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR AlphaFoldDB; F6ZT77; -.
DR STRING; 9258.ENSOANP00000015632; -.
DR Ensembl; ENSOANT00000015635.3; ENSOANP00000015632.3; ENSOANG00000009858.3.
DR eggNOG; KOG2408; Eukaryota.
DR GeneTree; ENSGT00940000158104; -.
DR HOGENOM; CLU_006087_1_0_1; -.
DR OMA; HPCFPIE; -.
DR TreeFam; TF314316; -.
DR UniPathway; UPA00194; -.
DR Proteomes; UP000002279; Chromosome X1.
DR Bgee; ENSOANG00000009858; Expressed in testis and 1 other cell type or tissue.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0004447; F:iodide peroxidase activity; IEA:UniProtKB-EC.
DR GO; GO:0042446; P:hormone biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006979; P:response to oxidative stress; IEA:InterPro.
DR GO; GO:0006590; P:thyroid hormone generation; IEA:UniProtKB-UniPathway.
DR CDD; cd00033; CCP; 1.
DR CDD; cd00054; EGF_CA; 1.
DR CDD; cd09825; thyroid_peroxidase; 1.
DR Gene3D; 2.10.70.10; Complement Module, domain 1; 1.
DR Gene3D; 1.10.640.10; Haem peroxidase domain superfamily, animal type; 1.
DR Gene3D; 2.10.25.10; Laminin; 1.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR019791; Haem_peroxidase_animal.
DR InterPro; IPR010255; Haem_peroxidase_sf.
DR InterPro; IPR037120; Haem_peroxidase_sf_animal.
DR InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR InterPro; IPR000436; Sushi_SCR_CCP_dom.
DR InterPro; IPR029589; TPO.
DR PANTHER; PTHR11475; OXIDASE/PEROXIDASE; 1.
DR PANTHER; PTHR11475:SF60; THYROID PEROXIDASE; 1.
DR Pfam; PF03098; An_peroxidase; 1.
DR Pfam; PF07645; EGF_CA; 1.
DR Pfam; PF00084; Sushi; 1.
DR PRINTS; PR00457; ANPEROXIDASE.
DR SMART; SM00032; CCP; 1.
DR SMART; SM00181; EGF; 1.
DR SMART; SM00179; EGF_CA; 1.
DR SUPFAM; SSF57535; Complement control module/SCR domain; 1.
DR SUPFAM; SSF57196; EGF/Laminin; 1.
DR SUPFAM; SSF48113; Heme-dependent peroxidases; 1.
DR PROSITE; PS00010; ASX_HYDROXYL; 1.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS50026; EGF_3; 1.
DR PROSITE; PS01187; EGF_CA; 1.
DR PROSITE; PS50292; PEROXIDASE_3; 1.
DR PROSITE; PS50923; SUSHI; 1.
PE 3: Inferred from homology;
KW Disulfide bond {ECO:0000256|ARBA:ARBA00023157};
KW EGF-like domain {ECO:0000256|ARBA:ARBA00022536, ECO:0000256|PROSITE-
KW ProRule:PRU00076};
KW Heme {ECO:0000256|ARBA:ARBA00022617, ECO:0000256|PIRSR:PIRSR619791-2};
KW Hydrogen peroxide {ECO:0000256|ARBA:ARBA00023324};
KW Iron {ECO:0000256|ARBA:ARBA00023004, ECO:0000256|PIRSR:PIRSR619791-2};
KW Metal-binding {ECO:0000256|PIRSR:PIRSR619791-2};
KW Oxidoreductase {ECO:0000256|ARBA:ARBA00023002};
KW Peroxidase {ECO:0000256|ARBA:ARBA00022559};
KW Reference proteome {ECO:0000313|Proteomes:UP000002279};
KW Signal {ECO:0000256|ARBA:ARBA00022729};
KW Sushi {ECO:0000256|ARBA:ARBA00022659, ECO:0000256|PROSITE-
KW ProRule:PRU00302};
KW Thyroid hormones biosynthesis {ECO:0000256|ARBA:ARBA00022534}.
FT DOMAIN 683..739
FT /note="Sushi"
FT /evidence="ECO:0000259|PROSITE:PS50923"
FT DOMAIN 739..782
FT /note="EGF-like"
FT /evidence="ECO:0000259|PROSITE:PS50026"
FT REGION 840..861
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 436
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000256|PIRSR:PIRSR619791-2"
SQ SEQUENCE 881 AA; 98652 MW; 77275A308B5653BC CRC64;
IYFMLNSLFA SYRNLKRREV TSPAQLFAFS KSPERASQDV SRAAEIMEAS VQAYKLAFSD
GLPSAVMNII ANVSGCLPFM LPPKCPNTCL ANKYRLITGA CNNRANPRWG GSNTALARWL
PAVYEDGISQ PKGWNPSTLY NGFALPMVRE VTRTIIQAPN EAVTEDNLYS DIMIVWGQYI
DHDIAFTPQS TSKATFLGGA DCDLTCENQN PCYPIQLPSN DSLSTRMDCL PFFRSSPACG
TGDQGAIFQN LSTSNPREQI NGLTSFLDAS TVYGSTPALE KKLRNWTHDE GLLRVNLQFS
DQGRAYLPFV SRVPSPCAQA RDTDRAERIE CFMAGDGRSS EVISLTALHT LWLREHNRLA
KALKQINPHW TSETLYQEAR KIVGALHQII TIRDYIPKII GPVAFEQYIG LYGGYDPTVN
PTVSNVFSTA AFRFGHATIH PVIKRLDARF QDHPDLPHLN LHEVFFSPWR IIKEGGLDPL
LRGLLAKSAK LQTQDQLMNE ELTEKLFVLS NSGALDLASL NLQRGRDHGL PGYNDWREFC
GFPRLKTRTD LNTAIANSSL VEKIMELYKH PDNIDVWLGG LVENFLPGAR TGPLFACIVG
RQMKALREGD RFWWENNDVF TDAQRRELGK HSLSRVICDN TGLDKVPGDA FRLGMFPRDF
ELCENTPGMN LAAWREDVHQ QVGTCGKPMK VENGDFLYCS ESGRPVVVYS CHHGYELQGH
EQLTCTNGRW DFKPPVCKDI NECEDEMNPS CHNSANCKNT KGGFYCACAD PYELGEDERT
CIGRPWSWQE CLLLDEQIII FHTADKGQSR HSNSRPLTPK PGLFPLSHAA SLNGGVDKNN
PAANSPCLPQ HSQSKKREEQ GPICSLKKNM VSFPWLFKLH L
//
